(1) Field of the Invention
The present invention relates to euthanasia compositions which are used for producing humane death in lower mammals. In particular the present invention relates to euthanasia solutions which contain the anesthetic gamma-hydroxybutramide (embutramide), a chloroquine or quinacrine compound and lidocaine or a salt thereof.
(2) Prior Art
Euthanasia compositions for lower mammals are necessary in order to provide humane death. Generally the solutions are injected intravenously or intraperitoneally. Users or user facilities of such solutions are animal control facilities, humane societies, veterinarians, veterinary hospitals, zoos and researchers. The owners of such animals are all concerned with providing humane death.
Euthanasia compositions containing barbiturates are on the market. These solutions are controlled by the U.S. Drug Enforcement Administration (DEA) because of the barbiturates which are Class II or Class III controlled substances. There is a need for compositions which are not controlled because of the record keeping involved in handling the barbiturate compositions.
The need to formulate a new euthanasia composition was prompted by problems with a euthanasia composition which was marketed under the name "T-61" and is no longer produced. It is comprised of an anesthetic, gamma-hydroxybutramide; a local anesthetic, tetracaine; a muscle relaxant, mebezonium; and a solvent, dimethylformamide. The composition of this solution contains as solids, 78% gamma-hydroxybutramide; 2% tetracaine (a local anesthetic); and 20% mebezonium, and as liquids a mixture of 60% dimethylformamide and 40% water. The solution contained 25.5% total solids and the solution has a non-viscous consistency and is injectable with a 22 gauge needle or larger.
A component of T-61 was causing adverse side effects when the product was rapidly injected intravenously. The physiological and pharmacological effects of each component of the euthanasia solution, T-61 were investigated. The anesthetic, gamma-hydroxybutramide, appeared to be an effective lethal drug at the recommended dose for T-61 (62 mg/kg). Its onset of action occurred within 15 to 25 seconds and has a smooth, calm induction with 47% ethanol used as an investigational vehicle. Mebezonium, the neuromuscular blocking agent included in T-61 was found to be effective at the concentration contained in T-61. The equi-effective dose of mebezonium is about 3 mg/kg and at the volume recommended for euthanasia with T-61, the dose of the muscle relaxant is 15 mg/kg IV. The onset of effect at the equi-effective dose is approximately 75 seconds.
Tetracaine hydrochloride (5 mg/ml; 1.5 mg/kg) appeared to be responsible for bizarre behavioral effects when T-61 was given rapidly. This dose is higher than those used for therapeutic purposes. This response, e.g., stiffening of the forelimbs, opisthotonos, and an apparent uneasy appearance was reproduced when tetracaine was given alone at the dose contained in T-61. This undesirable effect is most likely due to the direct stimulatory effects of tetracaine on the central nervous system. T-61 was recommended to be given slowly for this reason. In practice it was given rapidly and produced the undesired behavioral response. The euthanasia solutions approved by the FDA now for marketing do not allow a slow rate of injection since this is impractical in use.
Dimethylformamide (DMF) is the solvent used in T-61 to keep embutramide in solution. DMF is used at a 60% by volume in water concentration in T-61 and appears to have a local irritating effect at the site of injection. It also appears to have a central stimulating effect which is observed within the first 15 seconds following injection. This is then followed by a period of sedation lasting 15 to 30 minutes in some animals when given alone. It does not appear to alter the onset of anesthesia induced by embutramide nor contribute to the lethal effects of the anesthetic. DMF is most likely responsible for the discomfort induced when T-61 is given rapidly.
An additional problem with the T-61 composition is the appearance of a noticeable heart beat which persists during the euthanasia procedure. Although this activity of the heart is ineffective in perfusing body tissues, the heartbeat is nevertheless visible in thin chested dogs or small animals and usually persists for many minutes. This is not esthetically pleasing to the owner nor to people performing euthanasia.
Thus there is a need for an improved euthanasia solution. Gamma-hydroxybutramide is not included on the list of drugs controlled by the Federal Drug Enforcement Agency. In addition, it has a rapid onset of action causing almost immediate anesthesia and cessation of breathing. The problem then was to provide an effective formulation which overcomes the problems of the prior art with T-61.
The cardiac depressant and potential lethal effects of chloroquine and quinacrine are recognized. These drugs are used to treat malaria in human beings, but so far as is known, there has been no attempt to provide useful euthanasia formulations with these drugs.
In injectable formulations, the effects of high plasma concentrations of potassium on the heart is known. This can be seen in Mudge, G. H. and Weiner, I. M., Water, Salts and Ions. In Goodman and Gilman's The Pharmacological Basis of Therapeutics, Gilman, Rall, Nies and Taylor, Ed., New York, p 700, Pergamon Press, Inc. (1990).
In parent application Ser. No. 631,090, filed Dec. 19, 1990 gamma-hydroxybutramide and chloroquine or quinacrine compositions are described which are very effective in dogs. In cats the results were poor. Thus, there is a need for improved euthanasia compositions which are effective in cats, as well as other animals.